The invention concerns the use of a fluorocarbon as an agent for ophthalmology.
Within the meaning of this description, the term xe2x80x9cfluorocarbonxe2x80x9d either refers to compounds from the class of saturated, perfluorinated hydrocarbons in which all of the hydrogen atoms are replaced by fluorinated atoms, or partially fluorinated alkanes having the general formula RFRH or RFRHRF that can be present in a liquid or gel-like state. In this case, RF is a perfluorinated alkyl group and RH an alkyl group. Substances of this type, as well as their possible applications in medicine and technology are, for example, described in DE 42 05 341 A1, U.S. Pat. No. 5,275,669, U.S. Pat. No. 4,490,351, EP 493 677 A2 and DE 195 36 504 A1.
These fluorocarbons are almost always saturated with oxygen in a highly concentrated manner, whereby the oxygen is present in a physical solution. When increasing the partial pressure of the oxygen, fluorocarbons can store up to 50% by volume of oxygen. This compound-typical property was the basis for the development of numerous technical applications of these compounds (see the article by B. Cornils xe2x80x9cFluorous biphasic systemsxe2x80x9d in Angew. Chemie [Applied chemistry]1997, 109, 2147), as well as medical applications, e.g. as blood substitutes, as means for liquid artificial respiration, as oxygen carriers in ointments, etc. Fluorocarbons having a low content of dissolved oxygen spontaneously and very quickly absorb oxygen in contact with air until a balance between dissolved oxygen and the oxygen content of the ambient atmosphere is reached. These medical applications of fluorocarbons as oxygen carriers were described, for example, in the aforementioned publications and in the paper by K. C. Lowe xe2x80x9cProperties and Biomedical Applications of PFC and their Emulsionsxe2x80x9d, in Org. Fluorine Chem.: Principles and Commercial Appl., Plenum Press, N.Y. 1994.
Moreover, the application of fluorocarbons as an agent in ophthalmology has been described, for example, in the European Patent Application 563 446 A1. In particular, fluorocarbons are used as retina tampons when treating retinal detachments, where their density and their surface properties are of special significance.
So that it can be used as an ophthalmological agent via an intraoperative treatment, the fluorocarbons have to be left in the eye socket for a longer time instead of the vitreous body previously removed, e.g. in order to exert a constant, permanent pressure on the retina.
However, it has been shown that the known fluorocarbons can only be left in the eye for a limited period of time, see U.S. Pat. No. 5,037,384. That is, damage to the retina and the vessel system occur after only a short duration in the eye, the cause of which is to a great extent unknown and is, inter alia, attributed to the high density of the compounds. Due to the strong binding energy between carbon and fluorine, the fluorocarbons are chemically inert and are therefore not broken down by metabolical reactions.
To date, no importance has been ascribed to the quantity of oxygen usually dissolved in the fluorocarbons when the retina and adjacent intraocular structures are damaged. To the extent that this subject has been discussed at all in the literature, e.g. in the paper by A. J. Augustin, M. Spitznas, F. H. J. Koch, T. Bxc3x6ker, J. Lutz in Graefes Arch. Clin. Exp. Ophthalm. 1995, 233, 45-27, xe2x80x9cLocal Effects of Different Perfluorochemical Agentsxe2x80x9d, the conclusion was that the damage to the retina and the intraocular system observed in animal experiments had to be caused by other factors, e.g. by the tensides contained in the emulsions. This was reinforced in the paper which indicated that toxic effects could not be observed when using pure fluorocarbons (that nevertheless contained oxygen).
In other studies also, damage caused by fluorocarbons was ascribed to other properties of these substances and not to their dissolving power for oxygen. On the contrary, the oxygen solvency of these substances was repeatedly described as an advantage for ophthalmological applications.
Accordingly, this invention seeks to provide an agent for ophthalmology which can be used for a longer period of time than conventional fluorocarbons, with little or no damage to the retina and adjacent intraocular structures.
Thus, this invention provides an oxygen-physiologically acceptable fluorocarbon composition wherein the content of dissolved oxygen is less than 6%; and the fluorocarbon is chosen from compounds from the class of saturated, perfluorinated hydrocarbons in which all of the hydrogen atoms are replaced by fluorinated atoms, or partially fluorinated alkanes having the general formula RFRH or RFRHRF that can be present in a liquid or gel-like state. In this case, RF is a perfluorinated alkyl group and RH an alkyl group. In one embodiment, the mixture also contains 0 to 20% by volume of a second gas, such as carbon dioxide or nitric oxide.
This invention also provides a process of creating an oxygen-physiologically acceptable fluorocarbon composition, wherein the content of dissolved oxygen is less than 6%.
In another aspect, this invention provides the use of a physiologically acceptable fluorocarbon having a dissolved oxygen content of less than 6% by volume as an agent for ophthalmology. In particular, said fluorocarbon may be used as an intraocular agent, a retina tampon, an agent for treating ischemic retinal disorders, or as a vitreous body replacement.
An advantage of fluorocarbons having a dissolved oxygen content of less than 6% by volume is that it appears that they can be used as an ophthalmological agent for longer periods of time than conventional fluorocarbons, with little or no damage to the retina or intraocular structures.